I wonder if you watched a recent TV program on dogs, how derived from wolves they have become 'man's best friend'. Part of the film showed how quickly this can happen, as portrayed by Belyaev's experiment in Russia with silver foxes - which in surprisingly few generations of breeding became either 'lap-foxes' or vicious 'devils'. This was purely by selecting for character, and without time for genetic mutations. The 'lap-foxes' noses shortened, their face becoming rounded and more cuddly.

This evolutionary story is in keeping with the perception of a number of scientists, among them of course, Crawford and Marsh, whose Nutrition and Evolution you presumably have read! In the last decade or two, the effect of environment on genes is being revealed. The mechanisms of gene methylation and histone acetylation have come to light. These switches provide a way of fine-tuning the system for the environment, but in our increasingly artificial environment and accelerating changes we are leaning on them too much, and we are recognizing problems from our failure to respect their way of working. Until recently geneticists considered the germline in both male and female to be insulated from environmental effects so that the species was stabilized from one generation to another. Over past decade exceptions have been revealed. For one thing human epidemiological studies have been showing effects over several generations of famine, especially in relation to conception. Famine in the slow growth period before puberty, and smoking too, have transgenerational effects, some gender-line, and surprisingly others trans-gender. These studies indicate significant biochemical effects of nutrition and toxins on gene-switches. Not surprisingly hormones too have well-documented effects on gene-settings. Among perinatalists, the roles of endorphins and oxytocin in the process of bonding between baby and mother especially at birth, have been common knowledge for a decade or two. Less well-known is the work of a cytologist who studied cell-memory for 13 years and became a psychiatrist. It has taken epigenetics research to lower the skepticism that thousands of his teams' patients found themselves marked for life by their mother's emotional state around conception. Considering the amount of gene manipulation during the period of gametogenesis and fertilization, such vulnerability is scarcely surprising. Genomic imprinting is a series of processes whereby the embryo is established with certain gene settings from the father, others from the mother. Reproduction involves major epigenetic changes in the oocyte, first after it forms within the grandmother, then as it matures for ovulation. Imprinting of the spermatic genome happens on fertilization. Genomic imprinting of the embryo is complete by gastrulation, a week after implantation. Yet epigenetic changes due to environment will continue, though reducing as the person ages, changes are due to pollution, nutrition and lifestyle - nurture plays a powerful role. We need the greatest consideration of medical intervention in reproduction, such as IVF, caesarean section and so on. At short notice I have been asked to give a clue about my talk following the AGM. I intend to fill out this note and provide references then, and in the next issue. Human-beings may not, like the silver foxes be getting longer or shorter noses, but we are emphatically noticing other changes in their shape, and in mental soundness. These things can happen quickly. Meanwhile it is worth watching the media for signs of how the brain is subject to the way we are changing the biosphere, as will be brought out by our next speakers, Izzeldin and Takehira. Simon House

4. Some specific topics for preventive research yielding savings and improving national health

Previous recommendations

Low birthweight

Obesity

Gestational Diabetes

Pregnancy induced hypertension and pre-eclampsia

The cost of cancer

Mental ill-health

The Food system

5. The Counter Argument

6. Additional background comments

Skills are needed for stable employment

Numeracy and literacy

Figure 1. Numeracy and literacy skills To Eliminate Deprivation and Poverty - Start at the Beginning of Life

Figure 2. Babies born to parents in high-deprivation

7. Comment and conclusion

8. References

Overview on a major debate on prevention

Aneurin Bevan set up the National Health Service for the Atlee Government in 1948 with the aim that everybody would have access to the health care they needed regardless of income. The aspiration was that it would improve health in the UK and so reduce the need for the service.

The concept that "prevention is better than cure" appears since then, to have been mislaid.

a. The spending on preventive research accounts for only 2% of the total spend on medical research. The costs of heart disease, cancer and mental-ill health take up the highest proportion of the current £90.2 billion spending by the NHS which has risen from £55.8 billion in 2002-2003. The House considers the 2% spent on prevention is inadequate and that it should at least equal the spend on mechanisms and work related to the drug industry.

b. Sir David Cooksey's recommendation to reorganise health research will not deliver either the Prime Minister's wish for Medical Research to Reduce Costs of the National Health Service nor the public's aspiration to better health. This reduction is best achieved by prevention. That requires investment in research on how to prevent which is barely referenced in Sir David's recommendations (see discussion by the Chair and Dr. Evan Harris MP of the House of Common's Select Committee on Science and Technology below).

c. This House recommends that there should be a redesign of research funding to emphasize the importance of preventive research. This strategy should include at least:

(i) On Non-communicable Diseases: these now impose the highest cost to the health system. The epidemiology and historical evidence indicates that the large part of the cause of these diseases is nutritional and lifestyle and therefore are preventable. Advances made in reducing mortality have largely come from reduced smoking and management. There is a large gap in how to apply existing knowledge never mind developing the evidence base on prevention.

(ii) The Food System: The House recommends that a new Agricultural, Fishery and Food Research Council be created to include fisheries and oceanography. The primary objective should be nutrition and health.

1. Subject for debate

The present investment in research on prevention at 2% of the NHS and MRC research budget is inadequate.

That an increase in funding preventive research would be the surest way to cut costs in the NHS and enhance the health and prosperity of the nation.

That the level of preventive research funding by the Office for Strategic Coordination of Health Research (OSCHR) should be substantially increased over the next five years to reach equality to that which is devoted to drug discovery.

2.The case for the motion

In the Government's new direction for bio-medical research implemented 2007, prevention was not considered. It should be the priority if the aim is to reduce costs and improve health. The graphs below show the proportion spent on preventative research in the UK.

OSCHR: The new direction of Medical Research by MRC and NHS The new research strategy was laid down by Sir David Cooksey's Report to the Treasury 2006 with the formation of the Office for Strategic Coordination of Health Research (OSCHR) with the Government's aim of "better coordination of health research and more coherent funding arrangements" to reduce DH costs (Government's Response 2007). The report contains the following graph demonstrating the small proportion of research funding spent on prevention.

Prior to its implementation, Sir David presented his report to the Parliamentary Committee for Science and Technology chaired by the Rt Hon Phil Willis MP who, in his opening remarks, said:"a fairly widespread criticism (of the report and its recommendations) ... it seems to refer mainly to pharmaceuticals and not, for instance, to preventative medicine or health technologies. Why do they get so much less attention?"

The Rt Hon Dr. Evan Harris Q15 referred back to the Chair's comment adding concern over the effect of the "new institutional arrangements, to explain the sensitivities of people in research who feel they have to respond to a top-down diktat on research subjects". This would entrench "choosing pharmaceuticals as the main example of where you wanted to speed up the ability of investors to see fruition".

These comments by Dr Harris imply a problem with this seminal, policy-making document for bio-medical research as placing the emphasis on treatment with little attention to prevention.

3.Two related examples of the neglect of prevention

3.1. Low birthweight:

Despite the advances in science and medicine the prevalence of low birthweight has increased since 1953 and 1973 from 6.6% to 8% in 2005.

There is little or no Research Council effort of significance to define the cause and identify preventive measures. Low birthweight is a major cause of health inequality. It is the strongest predictor of risk to chronic ill health, heart disease, stroke and diabetes with learning and numeracy difficulties, behavioural pathology, poor skills, restricted job opportunities and crime. Severe neurodevelopmental disorder rises sharply as birthweight falls from about 1 /1,000 live births to over 200/1,000 below 1.5K*. These will be mostly premature deliveries. The consequences in disability impose a disproportionately high cost+ on the NHS and society because of the life long impact.

Poor maternal/fetal nutrition and living conditions is causatively linked to low birthweight regardless of socio-economic status, ethnicity or smoking habit1,2,3. A child born at low birthweight is likely to give birth to a similarly compromised child creating what is called the "Cycle of Deprivation" so perpetuating disadvantage4,5.

Cerebral Palsy alone costs £4 billion/year. About 50% of the cases are associated with low birthweight with the prevalence rising from 1 or 2 per 1,000 live births to over 200 per 1,000 at birthweights below 1.5 Kg. The Little Foundation initiated a European Research programme which has shown the majority is not due to mishap, obstetric or otherwise, but to adverse neurodevelopmental conditions during fetal brain development6. Yet there is no research of significance to define the cause and identify preventive measures.

* OPCS data

+With Courts awarding up to and over £4 million for alleged mishap, the cost of severe CNS damage associated with pregnancy and the perinatal condition is in the order of £4 to £8 billion/year.

3.2. Brain disorders and mental ill-health:

The cost of brain disorders and mental ill-health has been rising sharply. It has overtaken all other burdens of ill health. There is good evidence to implicate poor conditions at the start of life as a fundamental cause of disturbed development leading to high susceptibility to mental ill health. Moreover, mental ill health contributes to overall health inequalities that are very common and contribute significantly to other health risk behaviours like obesity, smoking, alcohol, substance abuse and also to physical illness.

The cost of mental health problems to this country is estimated at £77 billion in 2007 yet the impact of obesity being £4-£5 billion "is what is in most people minds ... it is equivalent to the whole of the funding for the NHS, so it is a huge impact, and it is about 4% added up of GDP calculated by Richard Layard±. The cost of brain disorders is greater than that of heart disease and cancer combined, the two most common causes of mortality from ill health.

The steepest rise in mental ill health is in young children. In 1972 it was predicted that brain disorders would rise following on the rise in death from heart disease7. The prediction was based on (i) the evidence based causal relationship considered to exist between hard, dietary fats and cardio-vascular disease, (ii) the dependence of brain development on prior vascular development, first in the placenta and then the fetus, and (iii) the similarity of nutritional requirements for specialized dietary fats for brain and vascular development and function. That prediction has been fulfilled with brain disorders having now overtaken all other burdens on ill health in the UK and in the 25 member states of the EU at 386 billion at 2004 prices8.

Lord Rea recently co-coordinated and chaired a consultation on nutrition and mental health9 which identified gaps in preventive research. The report refers to a Cochrane review by Lim10et al in 2006 which could not identify a single Randomised Clinical Trial in the dementias. It recommended that "Because of the major potential benefit for the fields of education, crime, health and well being of vulnerable sections of society, we believe more research is urgently needed in the area of nutrition and behaviour".

With the changes in food composition likely to be linked to the rise in brain disorders we are now faced with new and dangerous shift in the panorama of disease. The possibility that brain disorders will increase this century as heart disease did last is a real and sinister possibility.

4. Some specific topics for preventive research yielding savings and improving national health

There can be no more important time for investing in preventive research and practice than the present economic downturn. It is hoped that the motivation from this financial crisis can in this context, result in good for future generations by re-aligning research and practice towards the prevention, especially of the non-communicable disorders, and towards the enhancement of health and intelligence.

Previous recommendations:

The lack of preventive research and action is difficult to understand. Prevention in general, maternal nutrition, health and low birthweight featured in the Black report of 198011 and the subsequent the consultation paper by Sir Donald Acheson12, the Wanless Report 200213 and the Winterton Select Committee on Maternity Services (1990).

In the meantime, the incidence of low birthweight has risen since 1973 in the UK§ to be the highest in Western Europe, about the same as Romania and Kazakhstan, higher than Cuba 6% and twice that of Finland 4% and Samoa 4%. This inequality is at the root of much chronic ill health in the UK has occurred despite the advances in science and medicine referred to by Sir David Cooksey. Also at the root of such disorders are the wide spread alterations on food composition and resource deletion, such as the pollution and collapse of the fisheries, river, estuarine and coastal resources, which has adversely affected people in many Western countries.

§ Lord Warner in a reply to a PQ by Lord Morris: 6.6% in 1973, 7.6% in 2002, UNICEF has 8% in 2005.

Low birthweight: needs to be a high priority - see above.

Obesity: Prevention needs to start before and after birth with research on factors initiating the early drive to obesity around weaning. The role of various food production methods in creating obesogenic products needs attention in view of the change in food fat and fatty acid composition over the last decades.

Gestational diabetes: early detection could protect the mother and the fetus and subsequent risks of developing type II diabetes and heart disease. The incidence of both gestational and type II diabetes has been increasing, especially amongst immigrants.

Pregnancy induced hypertension and pre-eclampsia: A life threatening situation, the answer to which would contribute to the prevention of hypertension in the general population.

The cost of cancer: in the UK is £24 billion and heart disease £29 billion. Preventive approaches focused on smoking have had valuable effects. However, research on prevention, how to influence lifestyle, influence of food responsibility, how to target food production towards qualitative delivery for the heart and brain could all reduce this burden.

Mental ill health: see 3.2

The food system:

(i) The Agricultural and Food Research Council (AFRC) was closed with its then secretary, Sir William Henderson giving the reason that"its work has been a success story". Within a few years this view was falsified. The BSE epidemic demonstrated major gaps in knowledge as to the basics of how to feed herbivores and moreover about the brain with the result including the threat of CJD which is still an unanswered question. This, combined with public concern of infectious disease in the animal husbandry system and GM crops, led to the establishment of the Food Standard's Agency (FSA). However, that was designed to deal with food safety which is not the same as nutrition and health. It has, of late, by force of necessity, been moving closer to issues of nutrition and health, but it does not serve the purpose the AFRC did.

The British Biological Research Council (BBSRC) was supposed to fill gaps between the Medical Research Council (MRC) and FSA but again its priorities, as are those in the MRC, are different. The fact is that a doctor's medical practice has to deal with diabetes, heart disease, hypertension, mental ill health, stroke, cancer management, Crohn's, Coeliac disease, renal, liver failure, trauma and recovery from surgery to mention but a few of the non communicable disorders which have a major input from the principles of nutrition and health. To this list can be added low birthweight, obesity, gestational diabetes, pre-eclampsia pregnancy, infant feeding, school and hospital meals, elderly nutrition and management of disability such as cerebral palsy and war or accidental injury. The scope of improving health and disease prevention by simply finding out how to apply existing knowledge never mind the discovery of the new is immense. Yet many of these problems are growing (see 3.1).

(ii) The human genome is 1.5% different from the chimpanzee from whom the gene line is claimed to have separated 5 - 7 million years ago. That means that human physiology is adapted to wild foods. This simple fact is increasingly being recognized internationally as providing a pivotal guide to human nutrition and health. In the last century the intensification of crops and animals has led to major distortions in the food system. The sea food and fishery component of the historical diet remains as about the only part of the system that has not been radically changed in the interest of production; that however, has been eroded.

As an example, beef production now produces 4-6 times the calories from atherogenic and obesigenic fats compared to protein whereas the wild species produces more protein than fat. Poultry which in 1976 was recommended as a lean replacement of fatty red meat by the Royal College of Physicians and British Cardiac Society to help prevent heart disease, is no longer lean. Intensively reared chickens whether organic or not, produce some 2 to 3 times the fat calories over protein, facts which have been exposed in four TV programmes over the last two years. Yet it has been known since the 1950s that the excess fats from land based animals and their mimics used by the food industry were atherogenic and obesigenic. The converse has also been known that the marine, wild fats are protective as would indeed the original wild land based animal products. This history sits ill with the collapse of fisheries, especially in the UK in which its traditional use of marine exploitation led to "Rule Brittania".

5. The Counter Argument

"Life expectancy at birth in the UK has reached its highest level on record for both males and females"14. The human genome project and the advances in molecular biology have been making remarkable progress leading to the identification of genes responsible for disorder and gene clusters which are associated with diabetes, Alzheimer's Disease, cancer, Crohn's disease, macular degeneration, heart disease, and more. Almost every week a new identification is made including the unraveling variation in drug response. This new evidence heralds a new and powerful order of how we can deal with disease.

It may be possible to insert a gene, identify at an early stage the risk of an individual and make drug therapy more targeted and successful by assessing the response of the individual. Moreover, by identifying genetic risk for disease it raises the possibility of screening before or immediately after conception so that at first major gene disorders could be eliminated and then later, a disease free generation could be born. Moreover a new form of gene research is emerging in epigenetics whereby we are beginning to understand the way in which environmental conditions can set gene switches and affecting a subsequent generation. Indeed, it might be argued that the ultimate goal of such an approach includes both treatment and the prevention of disease.

Whilst this new dimension is to be applauded much of what is inherent in these discoveries is for tomorrow. There is an urgent need now to research into how we apply existing knowledge to address the issues referred to in 4.0 (i) and then expand the research into the improvement of preventive strategy. The gene defect for Cystic Fibrosis (CF) was discovered 21 years ago yet major advances have been achieved in the quality of life and life span of the children with CF and their families through management and nutrition. The same applies to phenyl-ketone-urea. What is proposed here is that the spending on how to apply such knowledge, learning from its application and research into further preventive measures, should at least be equal to that of the molecular biology approach. Unfortunately, the non communicable diseases are spreading worldwide. This country with its historical role in leadership still has a leadership role to play from, in this case, its biomedical and health research. The top 3 burdens of ill health worldwide are predicted to be (i) heart disease, (ii) adverse pregnancy outcome - (perinatal conditions) equal with (iii) mental ill health (www.globalforumhealth.org) by 2020.

What with the closure of the AFRC, nutrition today has been taken for granted. The truth is that our knowledge and understanding is superficial.

Despite the advance in longevity, the rise in brain disorders (3.2), which is escalating amongst children, probably poses the greatest health threat of recent time.

6. Additional background comments

The Cambridge University Group of Economic Historians spent 10 years in researching the rises and falls of economic prosperity since Roman times. Their results were published in a book. They concluded that the nutritional state of the population had been a consistent determinant of wealth (Sir Roderick Floud et al Health, Height and History, Cambridge University Press, 1990).

Skills are needed for stable employment: Industry increasingly demands skilled and qualified labour. This trend to skilled labour exacerbates the difficulty of those restricted by poor early development and hence entrenches the growth of poverty.

Skills Minister John Denham MP is reported to have pledged £4 billion into literacy and numeracy training for school leavers. However, this is closing the stable door after the horse has bolted. Though laudable, this approach can never raise the standard of the population when the potential for skills and learning is decided during brain development before birth and polished in the first few years after birth. Numeracy and literacy: The present situation in the
UK with regard to cognitive skills is not satisfactory (see histogram below).

Figure 1. Numeracy and literacy skills

To Eliminate Deprivation and Poverty - Start at the Beginning of Life

The reasons for the differences in figures 1 and 2 are not genetic! Therefore they are environmental with nutrition of school girls and young women as a major issue15. Poor cognitive abilities and learning difficulties are associated with very low birthweights16. In regions in Glasgow and the East-end of London the proportion of babies born at low birthweights can be as high as 14%. In our study area in East London it is about 10% with the number born small for gestational age between 16-20%.

Figure 2. Babies born to parents in high-deprivation areas are much more likely to be of low birthweight than those in low-deprivation areas.

Similar situations are likely to apply to other large inner city regions throughout the UK which has the worst record in Western Europe. Children so born are deprived of their full genetic potential for life with a waste in health costs, crime and loss to the economy and creative skills of the nation.

To Break the Chain: "We have written this book (Disadvantaged Children), to call attention to the health problems which underlies the school failure of impoverished children"17 This book was published in 1970 as good evidence was already there but there has been little response from Government despite several recommendations on the need for action.

The required recommendations have been voiced by the Black, Acheson and Wanless reports with the exception of addressing fundamental flaws in the food chain.

7. Comment and conclusion

The Foresight report on Brain Science does not mention nutrition. However, the Cabinet Office report 'Food matters' puts the cost saving from meeting national nutritional guidelines at £20 billion a year and 70,000 deaths. There is however, a question on how this can be achieved, what sort of nutrition is required and how can the industry and people be persuaded to follow new research results? Moreover the Government's concept of what is a balanced diet is a subject of research that needs to be done as the notions are vague and not always evidence based; what is the ω6/ω3 ratio for a balanced diet? If the priority in H. sapiens is the brain and the bran is mostly fat, what are the optimum requirements for women in their reproductive phase and for the infants and children?

Ofcom did a full cost/benefit analysis of introducing a 9pm watershed for HFSS television adverts and found that this could save up to £880 million a year (calculated in Quality Adjusted Life Years). This figure only takes into account changes in Children's exposure to advertising and doesn't attempt to quantify the much larger sum to be saved by the fall in adult's exposure to HFSS advertising from the same measure. Again there are many research questions around the issue of behaviour, health and food that could lead to preventive measures.

A study by the Government of Victoria compared the effect and cost effectiveness of various prevention / treatment method for obesity. Advertising restrictions came out as the most cost effective: http://www.health.vic.gov.au/healthpromotion/quality/ace_obesity.htm

The recognition of the importance of education of health and nutrition for school children and professionals (medical) was embedded in the Black report of 198018 and the subsequent the consultation paper by Sir Donald Acheson19, followed by the more recent Wanless Report 200220 and Lord Rea's report on nutrition and mental health, which recommended the development of nutritional science to the medical curriculum. These were important landmarks in providing the evidence and recommendations for addressing inequalities of health and the need for prevention in research and action.

The Lancet has claimed that lack of such action has resulted in a failure of public health strategy in the UK21. The reason for this failure is in part due to the lack of interest in preventive research in favour of discoveries related to drug discovery and genomic related research.

Foresight predicted that obesity, and related diseases, would cost the economy £45 billion by a year by 2050, and noted that this was a conservative estimate. The cost of mental ill health which is presently 50 times greater than obesity poses the most serious threat to human health.

2 Wynn, S.W., Wynn, A.H.A., Doyle, W. and Crawford, M.A. (1994) The association of maternal social class with maternal diet and the dimensions of babies in a population of London Women. Nutr. Health 9: 303 315.

13 Securing Our Future Health: Taking a Long-Term View, Derek Wanless, April 2002, "to deliver the highest quality over the next 20 years, the UK will need to devote more resources to health care and that this must be matched by reform to ensure that these resources are used effectively".

20 Securing Our Future Health: Taking a Long-Term View Derek Wanless, April 2002, "to deliver the highest quality over the next 20 years, the UK will need to devote more resources to health care and that this must be matched by reform to ensure that these resources are used effectively".

21 The Lancet. The catastrophic failures of public health. Lancet 2004; 363: 745.

Margaret (Peggy) Wynn died on the 8th January 2010. She was the devoted widow of Arthur Wynn, and co-author of many nutritional papers. Several were pathfinders in perinatal nutrition. Through my years of knowing Peggy and Arthur, I always enjoyed my visits to Church View, and was wonderfully welcomed and supported with their knowledge of the subject but also with their writing skills.